Virchows Archiv

, Volume 443, Issue 1, pp 57–66

Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening

  • Lars Morawietz
  • Thorsten Gehrke
  • Lars Frommelt
  • Petra Gratze
  • Andreas Bosio
  • Johannes Möller
  • Bernhard Gerstmayer
  • Veit Krenn
Original Article

Abstract

About 10% of hip endoprostheses will loosen after 10 years. Prosthesis loosening is caused by two different pathomechanisms: aseptic loosening (AL) and septic loosening (SL). This study evaluated differences in gene expression in AL and SL. Eight hybridizations were performed on PIQOR cDNA arrays. Objects of the study were periprosthetic interface tissue samples from two patients with SL and three patients with AL. Tissue parts directly adjacent to the site of RNA isolation were analyzed immuno/histopathologically in order to overcome the problem of tissue heterogeneity. Thirty-three genes were found constantly differentially expressed, among which were cd11b, cd18, cd68, osteopontin and ferritin heavy-chain upregulated in AL and collagen types 1alpha-1, 3alpha-1, integrin alpha-1, thrombospondin2 and nidogen upregulated in SL. The most striking finding was the strong upregulation (from 20-fold to 323-fold) of megakaryocyte stimulating factor (msf) in all aseptic cases and one of the two septic cases, which was confirmed by real-time reverse transcription-polymerase chain reaction. In this study, msf is linked to prosthesis loosening for the first time. The upregulation in AL suggests an important pathogenetic role: the msf splice product lubricin is responsible for the lubrication of healthy joints, but its excellent lubrication ability may disturb the tight interaction between bone and prosthesis and thereby contribute to prosthesis loosening.

Keywords

Aseptic prosthesis loosening Septic prosthesis loosening cDNA array msf Lubricin 

References

  1. 1.
    Armstrong LC, Bjorkblom B, Hankenson KD, Siadak AW, Stiles CE, Bornstein P (2002) Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a caspase-independent mechanism. Mol Biol Cell 13:1893–1905CrossRefPubMedGoogle Scholar
  2. 2.
    Berry DJ, Harmsen WS, Cabanela ME, Morrey BF (2002) Twenty-five-year survivorship of two thousand consecutive primary Charnley total hip replacements: factors affecting survivorship of acetabular and femoral components. J Bone Joint Surg Am 84:171–177Google Scholar
  3. 3.
    Boss JH, Shajrawi I, Mendes DG (1994) The nature of the bone-implant interface. Med Prog Technol 20:119–142PubMedGoogle Scholar
  4. 4.
    Case CP, Langkamer VG, Lock RJ, Perry MJ, Palmer MR, Kemp AJ (2000) Changes in the proportions of peripheral blood lymphocytes in patients with worn implants. J Bone Joint Surg Br 82:748–754CrossRefPubMedGoogle Scholar
  5. 5.
    Chen Y, Faraco J, Yin W, Germiller J, Francke U, Bonadio J (1993) Structure, chromosomal localization, and expression pattern of the murine Magp gene. J Biol Chem 268:27381–27389PubMedGoogle Scholar
  6. 6.
    Chomczynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15:532–537PubMedGoogle Scholar
  7. 7.
    Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genomewide expression patterns. Proc Natl Acad Sci U S A 95:14863–14868PubMedGoogle Scholar
  8. 8.
    Ekholm E, Hankenson KD, Uusitalo H, Hiltunen A, Gardner H, Heino J, Penttinen R (2002) Diminished callus size and cartilage synthesis in alpha 1 beta 1 integrin-deficient mice during bone fracture healing. Am J Pathol 160:1779–1785PubMedGoogle Scholar
  9. 9.
    Firestein GS, Pisetsky DS (2002) DNA microarrays: boundless technology or bound by technology? Guidelines for studies using microarray technology. Arthritis Rheum 46:859–861CrossRefPubMedGoogle Scholar
  10. 10.
    Flannery CR, Hughes CE, Schumacher BL, Tudor D, Aydelotte MB, Kuettner KE, Caterson B (1999) Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism. Biochem Biophys Res Commun 254:535–541PubMedGoogle Scholar
  11. 11.
    Gentzsch C, Kaiser E, Plutat J, Sellckau R, Wodtke J, Delling G (2002) CDNA array approach to cytokine expression profile of aseptic loosened hip arthroplasty. Pathologe 23:373–378CrossRefPubMedGoogle Scholar
  12. 12.
    Goldring SR, Jasty M, Roelke MS, Rourke CM, Bringhurst FR, Harris WH (1986) Formation of a synovial-like membrane at the bone-cement interface. Its role in bone resorption and implant loosening after total hip replacement. Arthritis Rheum 29:836–842PubMedGoogle Scholar
  13. 13.
    Hahn M, Vogel M, Schultz C, Niecke M, Delling G (1992) Histologic reactions of the bone-implant zone and cortical bone area after long-term hip replacement (in German). Chirurg 63:958–963PubMedGoogle Scholar
  14. 14.
    Harvard Health Letter Authors (2002) Arthritis. Hip replacement. Harv Health Lett 27:4–5Google Scholar
  15. 15.
    Jay GD, Britt DE, Cha CJ (2000) Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. J Rheumatol 27:594–600PubMedGoogle Scholar
  16. 16.
    Jay GD, Tantravahi U, Britt DE, Barrach HJ, Cha CJ (2001) Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (msf) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25. J Orthop Res 19:677–687CrossRefPubMedGoogle Scholar
  17. 17.
    Jellicoe PA, Cohen A, Campbell P (2002) Haemophilus parainfluenzae complicating total hip arthroplasty: a rapid failure. J Arthroplasty 17:114–116CrossRefPubMedGoogle Scholar
  18. 18.
    Lim JS, Lee SH, Lee E, Kang Y, Kim JW, Kim JK, Kim HH, Lee C, Kim SJ, Bai GH, Lee HG, Kim KD, Chung TW, Choe YK (1997) Differential expression of ferritin heavy chain in THP-1 cells infected with Mycobacterium bovis BCG. Biochem Mol Biol Int 43:981–988PubMedGoogle Scholar
  19. 19.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408PubMedGoogle Scholar
  20. 20.
    Maloney WJ, Smith RL (1996) Periprosthetic osteolysis in total hip arthroplasty: the role of particulate wear debris. Instr Course Lect 45:171–182PubMedGoogle Scholar
  21. 21.
    Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304CrossRefPubMedGoogle Scholar
  22. 22.
    Merberg DM, Fitz LJ, Temple P, Giannotti J, Murtha P, Fitzgerald M, Scaltreto J, Kelleher K, Preissner K, Kriz R, Jacobs K, Turner K (1993) A comparison of vitronectin and megakaryocyte stimulating factor. In: Preissner KT, Rosenblatt S, Kost C, Wegerhoff J, Mosher DF (eds) Biology of vitronectins and their receptors. Elsevier, New York, pp 45–52Google Scholar
  23. 23.
    Mills JC, Gordon JI (2001) A new approach for filtering noise from high-density oligonucleotide microarray datasets. Nucleic Acids Res 29:E72CrossRefPubMedGoogle Scholar
  24. 24.
    Mirra JM, Amstutz HC, Matos M, Gold R (1976) The pathology of the joint tissues and its clinical relevance in prosthesis failure. Clin Orthop 117:221–240PubMedGoogle Scholar
  25. 25.
    Monsinjon T, Gasque P, Ischenko A, Fontaine M (2001) C3A binds to the seven transmembrane anaphylatoxin receptor expressed by epithelial cells and triggers the production of IL-8. FEBS Lett 487:339–346CrossRefPubMedGoogle Scholar
  26. 26.
    Ortega-Andreu M, Rodriguez-Merchan EC, Aguera-Gavalda M (2002) Brucellosis as a cause of septic loosening of total hip arthroplasty. J Arthroplasty 17:384–387CrossRefPubMedGoogle Scholar
  27. 27.
    Pandey R, Drakoulakis E, Athanasou NA (1999) An assessment of the histological criteria used to diagnose infection in hip revision arthroplasty tissues. J Clin Pathol 52:118–123PubMedGoogle Scholar
  28. 28.
    Patarca R, Saavedra RA, Cantor H (1993) Molecular and cellular basis of genetic resistance to bacterial infection: the role of the early T-lymphocyte activation-1/osteopontin gene. Crit Rev Immunol 13:225–246PubMedGoogle Scholar
  29. 29.
    Plate KH, Breier G, Farrell CL, Risau W (1992) Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 67:529–534PubMedGoogle Scholar
  30. 30.
    Santavirta S, Sorsa T, Konttinen YT, Saari H, Eskola AS, Eisen AZ (1993) Role of mesenchymal collagenase in the loosening of total hip prosthesis. Clin Orthop 290:206–215PubMedGoogle Scholar
  31. 31.
    Savarino L, Granchi D, Ciapetti G, Stea S, Donati ME, Zinghi G, Fontanesi G, Rotini R, Montanaro L (1999) Effects of metal ions on white blood cells of patients with failed total joint arthroplasties. J Biomed Mater Res 47:543–550CrossRefPubMedGoogle Scholar
  32. 32.
    Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11:279–303PubMedGoogle Scholar
  33. 33.
    Swann DA, Hendren RB, Radin EL, Sotman SL, Duda EA (1981) The lubricating activity of synovial fluids. Arthritis Rheum 24:22–30PubMedGoogle Scholar
  34. 34.
    Swann DA, Silver FH, Slayter HS, Stafford W (1985) The molecular structure and lubricating ability of lubricin isolated from bovine and human synovial fluids Biochem J 225:195–201Google Scholar
  35. 35.
    Turner KJ, Fitz LJ, Temple P, Jacobs K, Larson D, Leary AC, Kelleher K, Giannotti J, Calvetti J, Fitzgerald M, Kriz MJ, Ferenz C, Grobholz J, Fraser H, Bean K, Norton CR, Gesner T, Bhatia S, Kriz R, Hewick R, Clark SC (1991) Purification, biochemical characterization, and cloning of a novel megakaryocyte stimulating factor that has megakaryocyte colony stimulating activity (abstract). Blood 78:279Google Scholar
  36. 36.
    van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536PubMedGoogle Scholar
  37. 37.
    Wei Y, Miller SC, Tsuji Y, Torti SV, Torti FM (1990) Interleukin 1 induces ferritin heavy chain in human muscle cells. Biochem Biophys Res Commun 169:289–296PubMedGoogle Scholar
  38. 38.
    Weyand CM, Geisler A, Brack A, Bolander ME, Goronzy JJ (1998) Oligoclonal T-cell proliferation and interferon-gamma production in periprosthetic inflammation. Lab Invest 78:677–685PubMedGoogle Scholar
  39. 39.
    Willert HG (1977) Reactions of the articular capsule to wear products of artificial joint prostheses. J Biomed Mater Res 11:157–164PubMedGoogle Scholar
  40. 40.
    Wooley PH, Fitzgerald RH, Song Z, Davis P, Whalen JD, Trumble S, Nasser S (1999) Proteins bound to polyethylene components in patients who have aseptic loosening after total joint arthroplasty. A preliminary report. J Bone Joint Surg Am 81:616–623PubMedGoogle Scholar
  41. 41.
    Yamaguchi S, Yamaguchi M, Yatsuyanagi E, Yun SS, Nakajima N, Madri JA, Sumpio BE (2002) Cyclic strain stimulates early growth response gene product 1-mediated expression of membrane type 1 matrix metalloproteinase in endothelium. Lab Invest 82:949–956PubMedGoogle Scholar
  42. 42.
    Yokohama Y, Matsumoto T, Hirakawa M, Kuroki Y, Fujimoto N, Imai K, Okada Y (1995) Production of matrix metalloproteinases at the bone-implant interface in loose total hip replacements. Lab Invest 73:899–911PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Lars Morawietz
    • 1
  • Thorsten Gehrke
    • 2
  • Lars Frommelt
    • 2
  • Petra Gratze
    • 1
  • Andreas Bosio
    • 3
  • Johannes Möller
    • 1
  • Bernhard Gerstmayer
    • 3
  • Veit Krenn
    • 1
  1. 1.Institute for Pathology, University Clinic CharitéCharité University Hospital, Humboldt University of BerlinBerlinGermany
  2. 2.ENDO-Klinik HamburgHamburgGermany
  3. 3.Memorec Stoffel GMBHCologneGermany

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